Amitriptyline – Uses and Dose

What is Amitriptyline?

Amitriptyline is a tricyclic antidepressant with sedative effects. Amitriptyline affects certain chemical messengers (neurotransmitters) that communicate between brain cells and help regulate mood. Amitriptyline is a prescription medicine used to treat symptoms of depression.

Brand names of Amitriptyline

Common brand names are Elavil, Endep, and Vanatrip

Storage

Recommended storage temperature: 2 – 8 °C. Keep in a dry place.

Identity of Amitriptyline

Type of medicine	Tricyclic antidepressants
Synonyms	Amitriptilina, Amitriptylin, Amitriptyline, Amitriptylinum
Molecular Formula	C20H23N
Molecular Weight	277.403 g/mol
IUPAC Names	3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine
Structural formula of main components
Pure active ingredient	Amitriptyline
Appearance	Crystals
Melting point	196 °C
pH	7.4
Solubility	Freely soluble in water

Uses of Amitriptyline

Amitriptyline is indicated for the treatment of major depressive disorder and neuropathic pain and for the prevention of migraine and chronic tension headache. It can be used for the treatment of nocturnal enuresis in children older than 6 after other treatments have failed.

Depression

Amitriptyline is effective for depression, but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability.

Pain

Amitriptyline alleviates painful diabetic neuropathy. It is recommended by a variety of guidelines as a first- or second-line treatment. It is as effective for this indication as gabapentin or pregabalin but less well tolerated.

Headache

Amitriptyline is probably effective for the prevention of periodic migraine in adults. Amitriptyline is similar in efficacy to venlafaxine and topiramate but carries a higher burden of adverse effects than topiramate.

Side Effects of Amitriptyline

Like all medicines, amitriptyline can cause side effects in some people, but many people have no side effects or only minor ones.

Some of the common side effects of amitriptyline gradually improve as your body gets used to the medicine.

Common side effects

Doses of amitriptyline for pain are lower than the doses for depression. This means the common side effects tend to be milder and go away within a few days.

Keep taking the medicine but talk to your doctor or pharmacist if these side effects bother you or do not go away:

• Constipation
• Dizziness
• Dry mouth
• Feeling sleepy
• Difficulty peeing
• Headache

Serious side effects

It happens rarely, but some people have a serious side effect after taking amitriptyline.

Call a doctor straight away if you have:

• A fast or irregular heartbeat
• Yellow skin, or the whites of your eyes go yellow – these can be signs of a liver problem
• A headache, feel confused or weak, or get muscle cramps – these can be signs of a low sodium level in your blood
• Thoughts about harming yourself or ending your life
• Eye pain, a change in your eyesight, swelling or redness in or around your eye

Mechanism of action

The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain. These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects. This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.

Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown

Drug interaction with other medicines

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/non-prescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug are: arbutamine, disulfiram, thyroid supplements, other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, “blood thinners” such as dabigatran/warfarin), anticholinergic drugs (such as belladonna alkaloids), certain drugs for high blood pressure (drugs that work in the brain such as clonidine, guanabenz).

Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.

Other medications can affect the removal of amitriptyline from your body, thereby affecting how amitriptyline works. These drugs include cimetidine, terbinafine, drugs to treat irregular heart rate (such as quinidine/propafenone/flecainide), antidepressants (such as SSRIs including paroxetine/fluoxetine/fluvoxamine). This is not a complete list.

Many drugs besides amitriptyline may affect the heart rhythm (QT prolongation in the EKG), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Before using amitriptyline, report all medications you are currently using to your doctor or pharmacist.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness, including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and opioid pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain decongestants or ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

Amitriptyline is very similar to nortriptyline. Do not use medications containing nortriptyline while using amitriptyline.

Dosage of Amitriptyline

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• Your age
• The condition being treated
• The severity of your condition
• Other medical conditions you have
• How you react to the first dose

Forms and strengths

Generic: Amitriptyline

• Form: oral tablet
• Strengths: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mgzq

Dosage for depression

Adult dosage (ages 18–64 years)

• Typical starting dosage: 75 mg per day, usually in divided doses.
• Dosage increases: Your doctor will slowly increase your dosage if needed.
• Maximum dosage: 150 mg per day.
• Alternative dosage regimen: Start with 50 to 100 mg at bedtime. This may be increased by 25 or 50 mg as needed in the bedtime dose, for a total of 150 mg per day.

Child dosage (ages 12–17 years)

Typical starting dosage: 10 mg three times a day with 20 mg at bedtime, for a total of 50 mg per day.

Child dosage (ages 0–11 years)

It hasn’t been confirmed that amitriptyline is safe and effective for use in children younger than 17 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Over dosage

Seek emergency medical attention or call the Poison Help line provided by your region or country. An overdose of amitriptyline can be fatal.

Symptoms of overdose may include:

• Irregular heartbeat
• Seizures
• Coma (loss of consciousness for a period of time)
• Confusion
• Problems concentrating
• Hallucinating (seeing things or hearing voices that do not exist)
• Agitation
• Drowsiness
• Rigid muscles
• Vomiting
• Fever
• Cold body temperature

Precautions of Amitriptyline

Before taking amitriptyline,

• Tell your doctor and pharmacist if you are allergic to amitriptyline or any other medications.
• Tell your doctor if you are taking cisapride (Propulsid) (not available in the U.S.) or monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have taken an MAO inhibitor during the past 14 days. Your doctor will probably tell you that you should not take amitriptyline.
• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: antihistamines; cimetidine (Tagamet); diet pills; disulfiram (Antabuse); guanethidine (Ismelin); ipratropium (Atrovent); quinidine (Quinidex); medications for irregular heartbeats such as flecainide (Tambocor) and propafenone (Rythmol); sleeping pills; thyroid medications; and tranquilizers.
• tell your doctor if you have recently had a heart attack. Your doctor will probably tell you not to take amitriptyline.
• tell your doctor if you drink large amounts of alcohol and if you have or have ever had glaucoma (an eye condition); an enlarged prostate (a male reproductive gland); difficulty urinating; seizures; an overactive thyroid gland (hyperthyroidism); diabetes; schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions); or liver, kidney, or heart disease.
• Tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking amitriptyline, call your doctor. Do not breast-feed while you are taking amitriptyline.
• Talk to your doctor about the risks and benefits of taking this medication if you are 65 years of age or older. Older adults should not usually take amitriptyline because it is not as safe or effective as other medication(s) that can be used to treat the same condition.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking amitriptyline.
• You should know that amitriptyline may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• Remember that alcohol can add to the drowsiness caused by this medication.

Fertility, pregnancy and breastfeeding

Amitriptyline doesn’t affect fertility in men or women.

However, some people have sex-related problems while taking amitriptyline, such as:

• Swollen breasts
• Vaginal bleeding
• Erectile and ejaculation problems.

These side effects aren’t common and should pass after a few weeks. If they don’t, and this worries you, speak to your doctor. They can see if another drug may work better.

If you’re a woman who has been through menopause, you should contact your doctor as soon as possible if you experience any vaginal bleeding.

Amitriptyline shouldn’t affect any type of contraception, including the combined pill and emergency contraception.

Amitriptyline generally isn’t recommended if you’re pregnant. Your doctor will only prescribe it if you’re pregnant, if the benefits outweigh the risks. If they don’t think it’s right for you, don’t worry, as they will suggest another treatment.

Only a small amount of amitriptyline passes into breast milk, but it’s recommended that you don’t take amitriptyline if you’re breastfeeding. If you would like to breastfeed, talk to your doctor. There may be other medicines you can take instead.